Mitochondrial Impairment in Muscle Insulin Resistance

• ClinicalTrials.gov Identifier: NCT00222924
• Recruitment Status: Completed
• First Posted: September 22, 2005
• Last Update Posted: December 19, 2007
• Sponsor: University of Pittsburgh
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by: University of Pittsburgh

Tracking Information

• First Submitted Date: September 20, 2005
• First Posted Date: September 22, 2005
• Last Update Posted Date: December 19, 2007
• Study Start Date: December 2003
• Primary Completion Date: Not Provided
• Current Primary Outcome Measures (submitted: September 20, 2005): To measure the functional capacity of mitochondria in skeletal muscle of those with T2DM and those at increased risk of developing T2DM
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: September 20, 2005): To assess whether exercise and diet can improve mitochondrial function and morphology.
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Mitochondrial Impairment in Muscle Insulin Resistance
• Official Title: Mitochondrial Impairment in Muscle Insulin Resistance
• Brief Summary: This investigation is being carried out to learn more about research findings from a study that was completed last year. Those findings revealed that within the skeletal muscle cells of individuals with type 2 diabetes, there was often damage to the mitochondria (the muscle cell's power source or the machinery of the muscle cell that produces energy). In individuals with type 2 diabetes, the liver continues to release sugar even when sugar levels are normal; the pancreas is not able to produce and release insulin normally; and the muscle and fat cells no longer respond as effectively to insulin. These defects lead to an abnormal rise of sugar in the blood. In this study, we want both to look more closely at the mitochondria and see if there is potential for improving mitochondrial functioning (improving the machinery of the muscle cell that produces energy) and reversing mitochondrial damage through a weight loss or a combined exercise/weight loss program. The program you get assigned to will be determined by a process called randomization (like a flip of a coin).

Detailed Description

Recent research from our laboratory has detected novel findings concerning damage to mitochondria within skeletal muscle in type 2 diabetes (type 2 DM), damage that is evident morphologically and by functional criteria. In this project, we propose, firstly, to more fully test this hypothesis of an impaired bio-energetic capacity, and to begin to examine the pathogenesis of damage to mitochondria in type 2 DM. We are also interested in assessing the potential for reversing damage, and improving functional capacity of mitochondria through a weight loss or a combined exercise and weight loss intervention.

The first specific aim is to measure the functional capacity of mitochondria in human skeletal muscle in type 2 DM and in those at apparent risk for type 2 DM (obese, sedentary, non-diabetic adults with the Metabolic Syndrome and/or impaired glucose tolerance). The second specific aim is to examine the morphology of mitochondria in human skeletal muscle in type 2 DM and in those at apparent risk for type 2 DM. The third specific aim is to examine the pathogenesis of mitochondrial damage in type 2 DM and in those at apparent risk for type 2 DM. The fourth specific aim is to assess whether exercise and diet can improve mitochondrial function and morphology in type 2 DM and in those at apparent risk for type 2 DM.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Factorial Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Diabetes
• Obesity

• Intervention: Behavioral: weight loss/ exercise
• Study Arms: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Enrollment (submitted: September 20, 2005): 49
• Original Enrollment: Same as current
• Actual Study Completion Date: December 2006
• Primary Completion Date: Not Provided

Eligibility Criteria

Inclusion Criteria:

• AGE 30 to 55 years old BMI 28 to 38 kg/m2 BLOOD PRESSURE Systolic < 150 ; Diastolic < 95 SEDENTARY Currently not engaged in a regular exercise program and a VO2 max pre-training value < 55 ml/kg-fat free mass-min HEALTH (Group 1) Type 2 diabetes mellitus for < 10 years and independent in SBGM HEALTH (Group 2) Non-diabetic with impaired glucose tolerance (as per ADA) or with Metabolic Syndrome (as per NCEP-ATP III)

HEALTH Must be in good general health with no known h/o the following:

liver disease, kidney disease, PVD (including diminished pulses, or H/O thrombophlebitis), heart disease (including any h/o MI), neuromuscular disease, neurological disease (including peripheral neuropathy or muscle wasting), paresis, edema , current malignancy, or any drug or alcohol abuse, LAB VALUES Enroll if: No Proteinuria (defined as < 1+ protein on routine dipstick) Hct > 34% ALT < 80, AST < 80, Alk Phos < 240 sTSH < 8 (Group 2) 2 hr glucose on OGTT >140mg/dl but < 200mg/dl or NCEP-ATP III criteria) Triglyceride < 450 Cholesterol < 300 Negative Urine Pregnancy

Exclusion Criteria:

• (Group 1) anti-hypertensives, "statin" hypolipemics, and diabetic medications okay but exclude if taking: insulin, or a hypolipemic that is not a "statin" (Group 2) "statin" hypolipemic medications are okay. A hypolipemic that is not a "statin" will exclude.

Inability and / or unwillingness to comply with the protocol as written Previous difficulty with lidocaine or other local anesthetic Claustrophobia Wt gain or loss of > 3 kg during past 4 weeks

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 30 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00222924
• Other Study ID Numbers: 021165; R01DK049200 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Not Provided
• Study Sponsor: University of Pittsburgh
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: David E. Kelley, MD; University of Pittsburgh

• PRS Account: University of Pittsburgh
• Verification Date: December 2007